MUC1 Vaccine in Conjunction With Poly-ICLC in Patients With Recurrent and/or Advanced Prostate Cancer

This is a one-arm clinical trial, to evaluate 2 doses of poly-ICLC for reversing systemic
immuno-suppression: 25 μg/kg and 50 μg/kg. These doses will be administered I.M. three times
a week for 2 weeks. Following 2 weeks of treatment with poly-ICLC alone, patients will be
immunized subcutaneously with the 100-mer MUC-1 peptide + GM-CSF. Subjects will be boosted
twice at two week intervals, and subsequently 3 months later, if they experience clinical
benefit or if they have clinically stable disease. Poly-ICLC will be administered
continually 3 times a week I.M. for the first 2 weeks and 2 times a week I.M. thereafter.
Subjects will continue on study until they have evidence of progressive disease. The primary
objective of this study is to evaluate the efficacy of Poly-ICLC in boosting the immunologic
response of a MUC1 vaccine. Secondary objectives are to evaluate a) changes in markers of
systemic immunosuppression; b) changes in dendritic cell number and function; and c)
clinical response. Up to 30 subjects will be enrolled in this single-site study.

Inclusion Criteria:

- 18 years of age or older and must have histologically confirmed adenocarcinoma of the
prostate with systemic disease are potentially eligible. Patients with an early
relapse must have undergone and failed definitive surgery and/or radiation. Patients
can either be hormone naive, may be on concurrent hormone therapy with LHRH
analogues, or may be hormone refractory (see section 3.1.4 of the full protocol)

- Must have evidence of systemic immunosuppression as evidenced by the presence of one
or more of the following: 1) Low or absent T cell zeta chain expression in peripheral
blood (PB), 2) Low level cytokine production ( i.e., IFN-gamma , IL-4 ) by T cells in
PB, 3) Upregulation of granulocyte activation markers (CD 15) in PB

- Availability of at least 2 PSA measurements over 2 to 6 weeks, clearly documenting a
rising PSA. The minimum rise in PSA must be at least 50% from baseline PSA. The last
of these PSA values must be > 2 .

- Patients may be hormone-refractory (rising PSA, despite castrate testosterone levels,
i.e., < 50 ng/ml); may have metastatic disease; and maybe on bisphosphonates. If
patients are on anti-androgens (Flutamide/Casodex), they must have been off of these
agents for at least 28 days prior to enrollment for flutamide, and at least 42 days
prior to enrollment for bicalutamide (Casodex)), without a drop in PSA. If hormone
refractory, patients will continue LHRH analogues.

- Signed written informed consent given by the patient before or at enrollment in the
study and following receipt of verbal and written information about the study.

- No concomitant therapy with steroids

- No other investigational therapy within 4 weeks of enrolling on this protocol

- No chemotherapy or radiation therapy within 6 weeks of enrolling on this protocol.

- ECOG performance status 0 or 1

- Patients must have adequate organ and marrow function

- Men must agree to use adequate contraception (hormonal or barrier method of birth
control) prior to study entry and for the duration of study participation.

Exclusion Criteria:

- Patients who have had chemotherapy or radiation therapy within 6 weeks of study
entry.

- No concurrent use of other investigational agents.

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Presence of an active acute or chronic infection, including urinary tract infection,
HIV (as determined by ELISA and confirmed by Western Blot) or viral hepatitis (as
determined by HBsAg and Hepatitis C serology). HIV patients are excluded based on
immunosuppression which may render them unable to respond to the vaccine; patients
with chronic hepatitis are excluded because of concern that hepatitis could be
exacerbated by the injections.

- Patients with either previously irradiated or new CNS (central nervous system)
metastases at entry are excluded. Pre-enrollment head CT is not required if not
indicated by clinical signs or symptoms.

- Patients with a history of auto-immune disease such as, but not restricted to,
inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis,
scleroderma, or multiple sclerosis.

- Subjects with active prior malignancy within the past 5 years (with exception of
non-melanoma skin cancers and carcinoma in situ of the bladder).